England number eight Ben Morgan has been ruled out of Saturday's RBS 6 Nations clash with Wales at the Millennium Stadium.
Morgan suffered an ankle injury during the opening-day victory over Scotland and had been pencilled in to return against Italy on Sunday, but head coach Stuart Lancaster has revealed he will miss the Grand Slam match.
"Ben will stay at Gloucester this week. We knew his ankle would take six to eight weeks and he won't make it in time," Lancaster said.
Lancaster is optimistic that locks Joe Launchbury, Geoff Parling and Courtney Lawes will recover from their respective elbow, shoulder and arm injuries to play in Cardiff.
Owen Farrell is fit to train having recovered from his quad injury and is expected to be restored at fly-half.
Lancaster believes the pressure-cooker environment of the Millennium Stadium, with England playing for the Grand Slam and Wales the title, will serve as ideal preparation for the rivals' group clash at the 2015 World Cup.
"It's a massive game because of the context of the result, which is huge for both teams," he added.
"We're a young team and a lot of our players haven't played there before, so going to that type of environment is exactly the test we want.
"It's a couple of years until 2015 and we know that we've got Wales in what will be a big high-pressure game.
"For a team to get that type of experience now and go up there and try to win a Grand Slam will be a special occasion."